Context-aware deep network for coronary artery stenosis classification in coronary CT angiography.

Automatic coronary artery stenosis grading plays an important role in the diagnosis of coronary artery disease. Due to the difficulty of learning the informative features from varying grades of stenosis, it is still a challenging task to identify coronary artery stenosis from coronary CT angiography (CCTA). In this paper, we propose a context-aware deep network (CADN) for coronary artery stenosis classification. The proposed method integrates 3D CNN with Transformer to improve the feature representation of coronary artery stenosis in CCTA. We evaluate the proposed method on a multicenter dataset (APOLLO study with NCT05509010). Experimental results show that our proposed method can achieve the accuracy of 0.84, 0.83, and 0.86 for stenosis diagnosis on the lesion, artery, and patient levels, respectively.

Association between mortality risk and the number, location, and sequence of subsequent fractures in the elderly.

The mortality risk showed a positive correlation as the number of subsequent fractures increased. Hip fracture showed the greatest association with mortality risk, followed by vertebral fracture. For the combination of hip and vertebral fracture, a hip fracture after a vertebral fracture showed the highest mortality risk. INTRODUCTION: It is unclear whether subsequent fractures or a certain location and sequence of subsequent fractures are associated with mortality risk in the elderly. We aimed to investigate the relationship between subsequent fractures and mortality risk. METHODS: Using the Korean National Health Insurance Research Database, we analyzed the cohort data of 24,756 patients aged > 60 years who sustained fractures between 2002 and 2013. Cox regression was used to assess the mortality risk associated with the number, locations, and sequences of subsequent fractures. RESULTS: Mortality hazard ratios (HRs) for women and men were shown to be associated with the number of subsequent fractures (one, 1.63 (95% confidence interval [CI], 1.48-1.80) and 1.42 (95% CI, 1.28-1.58); two, 1.75 (95% CI, 1.47-2.08) and 2.03 (95% CI, 1.69-2.43); three or more, 2.46(95% CI, 1.92-3.15) and 1.92 (95% CI, 1.34-2.74), respectively). For women, the mortality risk was high when hip (HR, 2.49; 95% CI, 1.80-3.44) or vertebral (HR, 1.40; 95% CI, 1.03-1.90) fracture occurred as a second fracture. Compared with a single hip fracture, there was a high mortality risk in the group with hip fracture after the first vertebral fracture (HR, 2.90; 95% CI, 1.86-4.54), followed by vertebral fracture after the first hip fracture (HR, 1.90; 95% CI, 1.12-3.22). CONCLUSION: The mortality risk showed a positive correlation as the number of subsequent fractures increased. Hip fracture showed the greatest association with mortality risk, followed by vertebral fracture. For the combination of hip and vertebral fracture, a hip fracture after a vertebral fracture showed the highest mortality risk.

Effect of alpine grazing on plasma and hair cortisol, serotonin, and DHEA in dairy cows and its welfare impact.

Through the analysis of blood and hair samples, this study evaluated the effects of grazing in alpine areas on welfare indices and indicators of stress in dairy cows. Twenty-one Holstein dairy cows (body weight: 637 ± 21.5 kg; days in milk: 133 ± 17.7, and second parity) were randomly assigned to 3 groups: control (nongrazing), 12 h of alpine grazing (12 hG), and 24 h of alpine grazing (24 hG). Blood samples for plasma collection were taken for 3 consecutive days at the end of the experiment. Hair samples were collected at the beginning and end of the experiment. Hormone measurements included cortisol, serotonin, and dehydroepiandrosterone (DHEA) in both plasma and hair samples. Plasma cortisol and DHEA levels did not differ among the 3 groups, whereas the plasma serotonin level was higher in the 24 hG group than that in the other groups. The plasma cortisol to DHEA ratio was lower in the 24 hG group than that in the control and 12 hG group. The hair samples taken at the end of the experiment showed that the cortisol level was significantly higher in the control group than that in both of the grazing groups and also higher in the 12 hG than that in the 24 hG group. Hair DHEA and serotonin levels were highest in the 24 hG group. The hair cortisol to DHEA ratio was significantly higher in the control group than that in the 12 hG and 24 hG groups and in the 12 hG group than that in the 24 hG group. Our study showed that grazing dairy cows in alpine areas for 24 h improved their welfare, as indicated by increased serotonin levels in hair and plasma, increased hair DHEA level, and decreased stress indicators, including the hair cortisol level and cortisol to DHEA ratio. Farm facilities should allocate optimal grazing time for optimal welfare of dairy cows.

Accessory Tragus: A Rare Congenital Anomaly in a Dog.

Accessory tragus is a congenital malformation of part of the external ear, commonly reported in humans. Clinically, it is a benign, cutaneous mass located anywhere between the tragus of the ear and the angle of the mouth, along the migratory path of the first branchial arch. An accessory tragus was diagnosed in an otherwise healthy six-month-old male castrated American pit bull terrier that had a haired, pedunculated cutaneous mass on the left maxillary region from birth. Histologically, the mass was a polypoid extension of histologically normal haired skin with a central core of subcutaneous adipose tissue and well-differentiated elastic cartilage. To the authors' knowledge, this is the first report of this lesion in a non-human species. Retrospective examination of records from 2008 to 2018 at the Washington Animal Disease Diagnostic Laboratory failed to identify any other case. As accessory tragus in humans is commonly linked with other congenital anomalies and syndromes, recognition of this lesion in animals may aid in early discovery of other congenital defects and inform adequate excision of the lesion to prevent chondrodermatitis.

Leukocyte-dependent effects of platelet-rich plasma on cartilage loss and thermal hyperalgesia in a mouse model of post-traumatic osteoarthritis.

OBJECTIVE: Platelet-rich plasma (PRP) is an emerging therapeutic strategy for treatment of osteoarthritis (OA); however, there is a lack of preclinical and clinical evidence for its efficacy and its mechanism of action is unclear. In the current study, we utilized leukocyte poor-PRP (LP-PRP) and leukocyte rich-PRP (LR-PRP) to mimic clinical point of care formulations and assessed their potential to alter disease progression in a mouse model of post-traumatic OA. METHOD: Three-month-old wild-type male FVB/N mice received destabilization of the medial meniscus (DMM) surgery to induce OA. To assess the efficacy of LP-PRP and LR-PRP, mice were given intraarticular injections at 2-, 7- and 28-days post-surgery. Mice were then assessed at 5-, 9-, and 13-weeks post-surgery for changes in chronic pain using the hot plate nociceptive assay. At 14-weeks, OA pathogenesis was evaluated using histology and phase-contrast µCT. RESULTS: Treatment with LP-PRP and to a lesser extent LR-PRP preserved cartilage volume and surface area compared to phosphate-buffered saline (PBS) as measured by phase-contrast µCT. However, both treatments had higher Osteoarthritis Research Society International (OARSI) and synovitis scores compared to sham, and neither substantially improved scores compared to PBS controls. With respect to thermal hyperalgesia, PBS-treated mice displayed reduced latency to response compared to sham, and LR-PRP but not LP-PRP improved latency to response at 5-, 9- and 13-weeks post-surgery compared to PBS. CONCLUSION: The results of this study suggest that effects of PRP therapy on OA progression and disease-induced hyperalgesia may be leukocyte-dependent. And while LP-PRP and to a lesser extent LR-PRP protect from volume and surface loss, significant pathology is still seen within OA joints. Future work is needed to understand how the different components of PRP effect OA pathogenesis and pain, and how these could be modified to achieve greater therapeutic efficacy.

Anthropogenic control over wintertime oxidation of atmospheric pollutants.

During winter in the mid-latitudes, photochemical oxidation is significantly slower than in summer and the main radical oxidants driving formation of secondary pollutants, such as fine particulate matter and ozone, remain uncertain, owing to a lack of observations in this season. Using airborne observations, we quantify the contribution of various oxidants on a regional basis during winter, enabling improved chemical descriptions of wintertime air pollution transformations. We show that 25-60% of NOx is converted to N2O5 via multiphase reactions between gas-phase nitrogen oxide reservoirs and aerosol particles, with ~93% reacting in the marine boundary layer to form >2.5 ppbv ClNO2. This results in >70% of the oxidizing capacity of polluted air during winter being controlled, not by typical photochemical reactions, but from these multiphase reactions and emissions of volatile organic compounds, such as HCHO, highlighting the control local anthropogenic emissions have on the oxidizing capacity of the polluted wintertime atmosphere.

Surgical Fixation of a Comminuted Inter-Trochanteric Fracture in a Patient with Bilateral Below Knee Amputation.

Surgical fixation of hip fractures in patients with below knee amputation is challenging due to the difficulty in obtaining optimal traction for reduction of the fracture. Surgeons may face difficulty in positioning such patients on the traction table due to the absence of the foot and distal lower limb. There are several techniques described to overcome this technical difficulty. In this case report, we present a case of a 64-year old gentleman with bilateral below knee amputation presenting with a comminuted right intertrochanteric fracture. We highlight a simple and effective method of applying skin traction to obtain adequate reduction for hip fracture fixation.

Effect of Scapular Stabilization Exercise during Standing on Upper Limb Function and Gait Ability of Stroke Patients.

BACKGROUND: The purpose of this study was to determine the effect of scapular stabilization exercise during standing on a paretic side on upper limb function and gait ability of stroke patients. METHODS: This study was a hospital-based, randomized controlled trial with a blinded assessor. A total of 17 patients with hemiplegic diagnosis after stroke were divided into two groups (9 patients in a study group and 8 patients in a control group). The study group received physical therapy and scapular stabilization exercise on a paretic side. Participants were subjected to initial evaluation before the treatment. Subjects were subsequently re-evaluated 4 and 8 weeks later to compare the changes. Measurements of hand function and gait ability were performed. RESULTS: Based on multivariate analysis of variance for repeated-measures, there was a significant time effect for Timed Up and Go test (TUG) (F = 13.816, P = 0.000), Functional Gait Assessment (FGA) (F = 18.613, P = 0.000), and manual function test (MFT) (F = 16.777, P = 0.000). The group × time interaction effect was also significant for FGA (F = 4.966, P = 0.024) and MFT (F = 6.946, P = 0.003), but not for TUG test (F = 3.343, P = 0.069). CONCLUSION: Results of the present study indicated that scapular stabilization exercise during standing on a paretic side for 8 weeks had an effect on hand function and gait ability of hemiplegic patients after stroke. Further studies are needed to find the most proper exercise for stroke patients who have gait disability and upper limb dysfunction.

Randomized clinical trial of antibiotic therapy for uncomplicated appendicitis.

BACKGROUND: Uncomplicated appendicitis may resolve spontaneously or require treatment with antibiotics or appendicectomy. The aim of this randomized trial was to compare the outcome of a non-antibiotic management strategy with that of antibiotic therapy in uncomplicated appendicitis. METHODS: Patients presenting to a university teaching hospital with CT-verified uncomplicated simple appendicitis (appendiceal diameter no larger than 11 mm and without any signs of perforation) were randomized to management with a no-antibiotic regimen with supportive care (intravenous fluids, analgesia and antipyretics as necessary) or a 4-day course of antibiotics with supportive care. The primary endpoint was rate of total treatment failure, defined as initial treatment failure within 1 month and recurrence of appendicitis during the follow-up period. RESULTS: Some 245 patients were randomized within the trial, and followed up for a median of 19 months. The duration of hospital stay was shorter (mean 3·1 versus 3·7 days; P < 0·001) and the medical costs lower (€1181 versus 1348; P < 0·001) among those randomized to therapy without antibiotics. There was no difference in total treatment failure rate between the groups: 29 of 124 (23·4 per cent) in the no-antibiotic group and 25 of 121 (20·7 per cent) in the antibiotic group (P = 0·609). Eighteen patients (9 in each group) had initial treatment failure, 15 of whom underwent appendicectomy and three received additional antibiotics. Thirty-six patients (20 in the no-antibiotic group, 16 in the antibiotic group) experienced recurrence, of whom 30 underwent appendicectomy and six received further antibiotics. CONCLUSION: Treatment failure rates in patients presenting with CT-confirmed uncomplicated appendicitis appeared similar among those receiving supportive care with either a no-antibiotic regimen or a 4-day course of antibiotics. Registration number: KCT0000124 ( http://cris.nih.go.kr).

Targeting 6-phosphogluconate dehydrogenase in the oxidative PPP sensitizes leukemia cells to antimalarial agent dihydroartemisinin.

The oxidative pentose phosphate pathway (PPP) is crucial for cancer cell metabolism and tumor growth. We recently reported that targeting a key oxidative PPP enzyme, 6-phosphogluconate dehydrogenase (6PGD), using our novel small-molecule 6PGD inhibitors Physcion and its derivative S3, shows anticancer effects. Notably, humans with genetic deficiency of either 6PGD or another oxidative PPP enzyme, glucose-6-phosphate dehydrogenase, exhibit non-immune hemolytic anemia upon exposure to aspirin and various antimalarial drugs. Inspired by these clinical observations, we examined the anticancer potential of combined treatment with 6PGD inhibitors and antimalarial drugs. We found that stable knockdown of 6PGD sensitizes leukemia cells to antimalarial agent dihydroartemisinin (DHA). Combined treatment with DHA and Physcion activates AMP-activated protein kinase, leading to synergistic inhibition of human leukemia cell viability. Moreover, our combined therapy synergistically attenuates tumor growth in xenograft nude mice injected with human K562 leukemia cells and cell viability of primary leukemia cells from human patients, but shows minimal toxicity to normal hematopoietic cells in mice as well as red blood cells and mononucleocytes from healthy human donors. Our findings reveal the potential for combined therapy using optimized doses of Physcion and DHA as a novel antileukemia treatment without inducing hemolysis.

Molecular Composition and Volatility of Organic Aerosol in the Southeastern U.S.: Implications for IEPOX Derived SOA.

We present measurements as part of the Southern Oxidant and Aerosol Study (SOAS) during which atmospheric aerosol particles were comprehensively characterized. We present results utilizing a Filter Inlet for Gases and AEROsol coupled to a chemical ionization mass spectrometer (CIMS). We focus on the volatility and composition of isoprene derived organic aerosol tracers and of the bulk organic aerosol. By utilizing the online volatility and molecular composition information provided by the FIGAERO-CIMS, we show that the vast majority of commonly reported molecular tracers of isoprene epoxydiol (IEPOX) derived secondary organic aerosol (SOA) is derived from thermal decomposition of accretion products or other low volatility organics having effective saturation vapor concentrations <10(-3) µg m(-3). In addition, while accounting for up to 30% of total submicrometer organic aerosol mass, the IEPOX-derived SOA has a higher volatility than the remaining bulk. That IEPOX-SOA, and more generally bulk organic aerosol in the Southeastern U.S. is comprised of effectively nonvolatile material has important implications for modeling SOA derived from isoprene, and for mechanistic interpretations of molecular tracer measurements. Our results show that partitioning theory performs well for 2-methyltetrols, once accretion product decomposition is taken into account. No significant partitioning delays due to aerosol phase or viscosity are observed, and no partitioning to particle-phase water or other unexplained mechanisms are needed to explain our results.

Formaldehyde production from isoprene oxidation across NOx regimes.

The chemical link between isoprene and formaldehyde (HCHO) is a strong, non-linear function of NOx (= NO + NO2). This relationship is a linchpin for top-down isoprene emission inventory verification from orbital HCHO column observations. It is also a benchmark for overall photochemical mechanism performance with regard to VOC oxidation. Using a comprehensive suite of airborne in situ observations over the Southeast U.S., we quantify HCHO production across the urban-rural spectrum. Analysis of isoprene and its major first-generation oxidation products allows us to define both a "prompt" yield of HCHO (molecules of HCHO produced per molecule of freshly-emitted isoprene) and the background HCHO mixing ratio (from oxidation of longer-lived hydrocarbons). Over the range of observed NOx values (roughly 0.1 - 2 ppbv), the prompt yield increases by a factor of 3 (from 0.3 to 0.9 ppbv ppbv-1), while background HCHO increases by a factor of 2 (from 1.6 to 3.3 ppbv). We apply the same method to evaluate the performance of both a global chemical transport model (AM3) and a measurement-constrained 0-D steady state box model. Both models reproduce the NOx dependence of the prompt HCHO yield, illustrating that models with updated isoprene oxidation mechanisms can adequately capture the link between HCHO and recent isoprene emissions. On the other hand, both models under-estimate background HCHO mixing ratios, suggesting missing HCHO precursors, inadequate representation of later-generation isoprene degradation and/or under-estimated hydroxyl radical concentrations. Detailed process rates from the box model simulation demonstrate a 3-fold increase in HCHO production across the range of observed NOx values, driven by a 100% increase in OH and a 40% increase in branching of organic peroxy radical reactions to produce HCHO.

Instrumentation and Measurement Strategy for the NOAA SENEX Aircraft Campaign as Part of the Southeast Atmosphere Study 2013.

Natural emissions of ozone-and-aerosol-precursor gases such as isoprene and monoterpenes are high in the southeast of the US. In addition, anthropogenic emissions are significant in the Southeast US and summertime photochemistry is rapid. The NOAA-led SENEX (Southeast Nexus) aircraft campaign was one of the major components of the Southeast Atmosphere Study (SAS) and was focused on studying the interactions between biogenic and anthropogenic emissions to form secondary pollutants. During SENEX, the NOAA WP-3D aircraft conducted 20 research flights between 27 May and 10 July 2013 based out of Smyrna, TN. Here we describe the experimental approach, the science goals and early results of the NOAA SENEX campaign. The aircraft, its capabilities and standard measurements are described. The instrument payload is summarized including detection limits, accuracy, precision and time resolutions for all gas-and-aerosol phase instruments. The inter-comparisons of compounds measured with multiple instruments on the NOAA WP-3D are presented and were all within the stated uncertainties, except two of the three NO2 measurements. The SENEX flights included day- and nighttime flights in the Southeast as well as flights over areas with intense shale gas extraction (Marcellus, Fayetteville and Haynesville shale). We present one example flight on 16 June 2013, which was a daytime flight over the Atlanta region, where several crosswind transects of plumes from the city and nearby point sources, such as power plants, paper mills and landfills, were flown. The area around Atlanta has large biogenic isoprene emissions, which provided an excellent case for studying the interactions between biogenic and anthropogenic emissions. In this example flight, chemistry in and outside the Atlanta plumes was observed for several hours after emission. The analysis of this flight showcases the strategies implemented to answer some of the main SENEX science questions.

Leptin-induced mitochondrial fusion mediates hepatic lipid accumulation.

BACKGROUND: Leptin alleviates metabolic conditions such as insulin resistance and obesity, although the precise mechanism of action is unclear. Mitochondrial fusion/fission states affect energy balance, but the association between mitochondrial fusion and lipid metabolism is also unknown. The aim of this study was to determine whether mitochondrial fusion/fission state regulates lipid accumulation and to understand the role of leptin in mitochondrial function and its mechanism of action in metabolic regulation. METHODS: Primary mouse hepatocytes were isolated from C57BL/6J mice and treated with leptin (25 ng ml(-1)) for 3 days before determinations of mitochondrial morphology and fatty acid accumulation. Hyperglycemia in C57BL/6J mice was induced by providing a 30% fructose-rich diet (FRD) for 6 months, followed by intraperitoneal injections of leptin (1 mg kg(-1) per body weight) for 6 weeks (twice per week). RESULTS: Leptin triggered mitochondrial fusion and alleviated high glucose-induced fatty acid accumulation in primary hepatocytes by promoting mitochondrial fusion-associated transcription factor peroxisome proliferative-activated receptor-α and co-activator peroxisome proliferative-activated receptor-γ co-activator (PGC)-1α. In turn, these activate the fusion protein mitofusin 1 (Mfn-1). RNA silencing of Mfn-1 or PGC-1 blocked the inhibitory effect of leptin. Leptin treatment also elevated liver Mfn-1 and PGC-1α and improved lipid profiles in FRD mice. CONCLUSIONS: Mitochondrial fusion has a critical role in alleviating hepatic fatty acid accumulation. Leptin switches mitochondrial morphology via a PGC-1α-dependent pathway to improve hyperlipidemia.

The orally active urotensin receptor antagonist, KR36676, attenuates cellular and cardiac hypertrophy.

BACKGROUND AND PURPOSE: Blockade of the actions of urotensin-II (U-II) mediated by the urotensin (UT) receptor should improve cardiac function and prevent cardiac remodelling in cardiovascular disease. Here, we have evaluated the pharmacological properties of the recently identified UT receptor antagonist, 2-(6,7-dichloro-3-oxo-2H-benzo[b][1,4]oxazin-4(3H)-yl)-N-methyl-N-(2-(pyrrolidin-1-yl)-1-(4-(thiophen-3-yl)phenyl) ethyl)acetamide (KR36676). EXPERIMENTAL APPROACH: Pharmacological properties of KR36676 were studied in a range of in vitro assays (receptor binding, calcium mobilization, stress fibre formation, cellular hypertrophy) and in vivo animal models such as cardiac hypertrophy induced by transverse aortic constriction (TAC) or myocardial infarction (MI). KEY RESULTS: KR36676 displayed high binding affinity for the UT receptor (Ki : 0.7 nM), similar to that of U-II (0.4 nM), and was a potent antagonist at that receptor (IC50 : 4.0 nM). U-II-induced stress fibre formation and cellular hypertrophy were significantly inhibited with low concentrations of KR36676 (≥0.01 µM). Oral administration of KR36676 (30 mg·kg(-1) ) in a TAC model in mice attenuated cardiac hypertrophy and myocardial fibrosis. Moreover, KR36676 restored cardiac function and myocyte size in rats with MI-induced cardiac hypertrophy. CONCLUSIONS AND IMPLICATIONS: A highly potent UT receptor antagonist exerted anti-hypertrophic effects not only in infarcted rat hearts but also in pressure-overloaded mouse hearts. KR36676 could be a valuable pharmacological tool in elucidating the complicated physiological role of U-II and UT receptors in cardiac hypertrophy.

Biphasic motion of the median nerve in the normal Asian population.

BACKGROUND: The biomechanical interaction between the median nerve and the flexor tendons is an important consideration in Carpal tunnel syndrome (CTS). We aim to quantify the displacement and compressive deformation pattern of the median nerve in various stages of finger flexion in the normal population at the inlet of the carpal tunnel. METHODS: Transverse ultrasounds images were taken at the carpal tunnel inlet during full-extension, mid-flexion and full flexion. The displacement, distance, Feret's diameter, and perimeter of the median nerve were calculated and compared between each position. RESULTS: Biphasic median nerve motion was observed, with a displacement of 2.84 ± 3.49 mm in the ulnar direction from full-extension to mid-flexion (Phase I) and a further 0.93 ± 3.04 mm from mid-flexion to full flexion (Phase II). Of 49 hands, 37 (75.5%) exhibited ulnar displacement in Phase I while 12 (24.5%) exhibited radial displacement. Feret's diameter (5.95 ± 1.08 mm) and perimeter (13.28 ± 2.09) of the median nerve were greatest in the mid-flexed position. CONCLUSION: In a healthy Asian population, the median nerve has a biphasic motion during finger flexion, with maximal deformation in the mid-flexed position.

PCDHB14- and GABRB1-like nervous system developmental genes are altered during early neuronal differentiation of NCCIT cells treated with ethanol.

Ethanol (EtOH) exposure during embryonic development causes dysfunction of the central nervous system (CNS). Here, we examined the effects of chronic EtOH on gene expression during early stages of neuronal differentiation. Human embryonic carcinoma (NCCIT) cells were differentiated into neuronal precursors/lineages in the presence or absence of EtOH and folic acid. Gene expression profiling and pathway analysis demonstrated that EtOH deregulates many genes and pathways that are involved in early brain development. EtOH exposure downregulated several important genes, such as PCDHB14, GABRB1, CTNND2, NAV3, RALDH1, and OPN5, which are involved in CNS development, synapse assembly, synaptic transmission, and neurotransmitter receptor activity. GeneGo pathway analysis revealed that the deregulated genes mapped to disease pathways that were relevant to fetal alcohol spectrum disorders (FASD, such as neurotic disorders, epilepsy, and alcohol-related disorders). In conclusion, these findings suggest that the impairment of the neurological system or suboptimal synapse formation resulting from EtOH exposure could underlie the neurodevelopmental disorders in individuals with FASD.

A cross-sectional multicenter study of osteogenesis imperfecta in North America - results from the linked clinical research centers.

Osteogenesis imperfecta (OI) is the most common skeletal dysplasia that predisposes to recurrent fractures and bone deformities. In spite of significant advances in understanding the genetic basis of OI, there have been no large-scale natural history studies. To better understand the natural history and improve the care of patients, a network of Linked Clinical Research Centers (LCRC) was established. Subjects with OI were enrolled in a longitudinal study, and in this report, we present cross-sectional data on the largest cohort of OI subjects (n = 544). OI type III subjects had higher prevalence of dentinogenesis imperfecta, severe scoliosis, and long bone deformities as compared to those with OI types I and IV. Whereas the mean lumbar spine area bone mineral density (LS aBMD) was low across all OI subtypes, those with more severe forms had lower bone mass. Molecular testing may help predict the subtype in type I collagen-related OI. Analysis of such well-collected and unbiased data in OI can not only help answering questions that are relevant to patient care but also foster hypothesis-driven research, especially in the context of 'phenotypic expansion' driven by next-generation sequencing.

Failure mode and effects analysis of the universal anaesthesia machine in two tertiary care hospitals in Sierra Leone.

BACKGROUND: Anaesthesia care in developed countries involves sophisticated technology and experienced providers. However, advanced machines may be inoperable or fail frequently when placed into the austere medical environment of a developing country. Failure mode and effects analysis (FMEA) is a method for engaging local staff in identifying real or potential breakdowns in processes or work systems and to develop strategies to mitigate risks. METHODS: Nurse anaesthetists from the two tertiary care hospitals in Freetown, Sierra Leone, participated in three sessions moderated by a human factors specialist and an anaesthesiologist. Sessions were audio recorded, and group discussion graphically mapped by the session facilitator for analysis and commentary. These sessions sought to identify potential barriers to implementing an anaesthesia machine designed for austere medical environments-the universal anaesthesia machine (UAM)--and also engaging local nurse anaesthetists in identifying potential solutions to these barriers. RESULTS: Participating Sierra Leonean clinicians identified five main categories of failure modes (resource availability, environmental issues, staff knowledge and attitudes, and workload and staffing issues) and four categories of mitigation strategies (resource management plans, engaging and educating stakeholders, peer support for new machine use, and collectively advocating for needed resources). CONCLUSIONS: We identified factors that may limit the impact of a UAM and devised likely effective strategies for mitigating those risks.